Manufacture of derivatives of disubstituted methane compounds



Patented May 29, 1951 MANUFACTURE OF DERIVATIVES F DISUB- STITUTED METHANE COMPOUNDS Sheila Edith Bywater, Heston, and Gordon James Pritchard, Halewood, Liverpool, England, assignorsto Ward, Blenkinsop & Company Limited, London, England, a British company No Drawing. Application June 23, 1947, Serial No. 756,563. In Great Britain November 17,

Section 1, Public Law 690, August 8, 1946 Patent expires November 17, 1964 13 Claims. 1

This invention is concerned with improvements in and relating to the manufacture of derivatives of disubstituted methane compounds, and it relates more particularly to the preparation of new derivatives of compounds of the general formula R1-CH2R2, (hereinafter referred to as D. S. M. compounds) in which R1 and R2, which may either be identical or different, are chosen from the residues of the following classes of substances:

A phenol sulphonic acid,

An alkyl phenol sulphonic acid,

A carboxyl phenol sulphonic acid,

A diphenyl or alkyl diphenyl monoor disulphonic acid,

A benzene sulphonic acid,

A sulpho benzoic acid,

A naphthalene or alkylnaphthalene monoor disulphonic acid,

A naphthol or alkyl naphthol sulphonicacid, or

A nuclear substituted halogen, amino or nitro derivative of any of the above substances.

These D. S. M. compounds are substances of the synthetic tanning material type, and British Patent No. 547,564 describes the preparation for medical and like uses of substances prepared by combining D. S. M. compounds with bactericidal and/or physiologically useful organic bases or with the hydrate or oxide of one or more of the metals zinc, bismuth, copper and mercury so as to form salts. A further development of this work is described in British Patent No. 552,751 which discloses the preparation of silver and/or lead derivatives of D. S. M. compounds, these metals being known to possess antiseptic properties. Thesaid prior specifications explain how substances prepared by combining a D. S. M. compound having tanning properties with abactericidal or antiseptic component can be used advantageously for medical and allied purposes inter alia because the tanning action of the D. S. M. component enables the bactericidal or antiseptic component to be fixed and held in the skin or tissue.

We have now found that a further series of new and valuable derivatives of D. S.'M. compounds can be produced by combining them with organometallic compounds of the undermentioned general formula.

Many of these organometallic compounds have valuable bactericidal, fungicidal, insecticidal or other useful properties, and we have found that by combining such compounds with D. S. M.

compounds products are obtained which have an extended field of usefulness compared with those of the products described in the said prior specifications and which can be used with advantage for many purposes, such for example as in agriculture, horticulture, the preservation of timber, in the textile industry, as well as in medicine and pharmacy. According to the invention therefore we prepare new and useful products by treating a D. S. M. compound, as herein defined, with an organometallic compound having useful properties and of the general formula RsMA, where R3 is an alkyl, aryl, aralkyl or heterocyclic radicle which may or may not be substituted with neutral, acidic or basic substituents, M is a polyvalent metal, preferably mercury or arsenic, and A is an acidic radicle such as halide, nitrate, acetate or hydroxide or oxide or (when R3 is basic or contains a basic substituent) an atomic grouping forming with M an acidic radicle and of such a nature that the compound will react with the D. S. M. compound, and irrespective of whether the said group is or is not split olf in the process of the formation of the D. S. M. organometallic compound.

Whilst we do not desire to be limited by any theoretical explanations, it may be said that the reaction which occurs appears to be one of salt formation and this may as stated above occur either with or without elimination or splitting off of the group or element A. It is clear that the reaction can take place in several ways all falling within the scope of the invention. Thus, in the simple case of the example given below, it is probable that the reaction can be represented by the following equation, in which R-SOsH has been Written for R1 and R SO3I-I for R2 in the general formula set out above: HO3SRCH2R1SO3H+2R3MA= R3M-O3SR-Ch2-R SO3MR3+2HA It will be seen that in this case the group or radicle A is split off, but if R3 were basic or had a basic substituent, as for example in the case of pyridyl group, the radicle A might or might not be split off.

If, for example RsMA were pyridyl mercuric I chloride, it is unlikely that the chlorine would be eliminated, 'at any rate completely, and the resulting reaction might be wholly or partly represented thus:

If, on the other hand, R3MA were to be pyridyl mercuric acetate, it is probable that both reactions would occur, depending on the reaction conditions, such for example as pH.

In general it may however be said that the organometallic compound RsMA should be one of basic function, which may, but need not necessarily, be centred on the metallic atom. In the cases of the stated mercury compounds, the basic function is centred on the M atom, but the use of other compounds such for example as an amino phenyl-arsonic acid, in which it is not so centred would of course also fall within the scope of the invention.

Whilst of course the invention comprises the production of the new substances in solid form, it is not limited to the carrying out of the reaction with stoichiometric proportions of the reaction components, and important advantages can, according to the invention, be secured by departing from such proportions.

It has hitherto been a drawback to the general use of organometallic compounds, particularly the aryl mercury compounds, that their solubilities in water and aqueous solutions, and in the commoner organic solvents are too low for satisfactory application of the compounds.

We have found that the new compounds are readily soluble, in an excess of the D. S. M. compounds from which they have been prepared, or in other D. S. M. compounds as well as in an excess of the parent sulphonic acids corresponding to R1 and R2, and this property enables the new compounds to be prepared in the form of solutions, suitable for application either as such or after dilution with water if necessary.

In general we have found that a pH value of from 4-65 is usually advantageous, and this can conveniently be attained by a suitable adjustment of the quantities of the above-mentioned solubilising substances; it should however be noted that the use of other substances, such for example as mineral acids for the purpose of pH adjustment would not fall outside the scope of the invention.

The desired effect can be achieved either by first preparing the solid compound and then dissolving it in a suitable quantity of the selected solubilising agent or agents, so as to produce a solution of the desired strength and pH value, or the composition of the reaction mixture can be so adjusted as to yield a solution of the new compound after completion of the reaction, any necessary adjustment of pH value being subsequently carried out.

Accordingly the invention also comprises a method of manufacturing a solution of a D. S. M./organometallic compound prepared by the above mentioned method either in an excess of the same D. S. M. compound or in one or more of the following: Solutions of one or more D. S. M. compounds other than the one used for the preparation of the D. S. M./organometallic compound or of one or more of the acids corresponding to R1 or R2 either with or without the addition of one or more mineral acids.

The invention also comprises the adjustment of the pH value of such solutions to from 46.5.

In order to facilitate a better understanding of the invention, the following examples of how it may be carried out are given only as illustrations:

Example I 1.37 parts by weight of phenyl mercuric hydroxide was boiled with water until solution was complete, and to this was added, drop by drop, 3.8 parts by weight of the D. S. M. condensation product of naphthalene-2-sulphonic acid and formaldehyde (prepared by the method disclosed in British Patent No. 547,564) in 28% concentration. When the equivalent amount had been thus added a gelatinous precipitate was thrown down, and the solution was found to be acid to Congo red paper. At this stage the solution is unfilterable, but when a further 10% excess (0.38 part by weight) of D. S. M. compound had been added in the same way, the insoluble material coagulated and was separated and dried, yielding 1.1 parts by weight.

. Per cent Found, Hg; 40.35 C33H24OsS2Hg2 the neutral salt requires C45H3sOaS2Hg4. the basic salt requires l-lg 51.1

Alternatively 14.5 parts by weight of phenyl mercuric acetate (2 mol) was dissolved in 400 parts by weight of hot absolute alcohol; the solution was then treated with a little charcoal and filtered. To the hot alcoholic solution 26.5 parts by weight of the D. S. M. condensation product of naphthalene-Z-sulphonic acid and formaldehyde in 35% concentration (1 mol) was added with stirring, a thick gelatinous precipitate separated which, after standing two hours, was filtered off and dried; yielding 8.2 parts by weight of the phenyl mercury complex. By concentrating the alcoholic mother liquors a further 5.9 parts by weight was obtained,

Per cent Found, Hg 44.0 C33H24O6S2Hg2 the true salt requires Hg 40.9 C45H3sOsS2Hg4 the basic salt requires Hg 51.1

The compound with Hg 44% is consistently obtained and is evidently a complex corresponding to neither of the theoretical salts.

This phenyl mercury complex was a buff powder and dissolved to give a 13.5% solution in a 35% aqueous solution of bis-(naphthalene-Z- sulphonic acid)-methane; this could be diluted without developing instability to form a solution containing 1 phenyl-mercury complex, with the pH adjusted to 4.0-4.5; this solution was then diluted 1000 times, the pH readjusted and the solution introduced into timber by the full cell process. The product was resistant to most of the common fungi.

In a similar manner the basic salt was isolated. 8.0 parts by weight of phenyl mercuric acetate (4 mols) was dissolvedin parts by weight of hot absolute alcohol, the solution was treated with a little charcoal and filtered, to the hot alcoholic solution 7.3 parts by weight of the D. S. M. condensation product of naphthalene-Z-sulphonic acid and formaldehyde in 35% concentration (1 mol) was added, the phenyl mercury complex was thrown down, and after filtering and concentrating the alcoholic mother liquors a total of 6.0 parts by weight of the phenyl mercury complex was obtained.

Per cent Found, Hg 51.2 C45H3sOsS2Hg4 the basic salt requires Hg 51.1 C33H2406S2Hg2 the true salt requires Hg 40.9

The basic phenyl mercury complex was a buff powder which dissolved to give a 0.5% solution in a 10% aqueous solution of either bis-(naphthalene-2-sulphonic acid) -methane, or naphthalene-2-sulphonic acid.

This solution without dilution was found to be suitable for the impregnation of timber, using the empty cell process.

Example II 6.72 parts by weight of phenyl mercuric acetate was dissolved in 120 parts by weight of hot absolute alcohol and 17.9 parts by weight of 10.1%

aqueous solution acid) -methane.

The phenyl mercury complex separated, and after the alcoholic solution had cooled, was filtered oil and dried.

of bis-(phenol-4-sulphonic Example III 8.06 parts by weight of phenyl mercuric acetate was dissolved in 160 parts by weight of hot ethyl alcohol and 10.7 parts by weight of 16.5% aqueous solution of bis-(naphthalene-2zl-disulphonic acid) -methane prepared by the method disclosed in British Patent No. 547,564 added. The phenyl mercury complex separated and was filtered off and dried. 6.3 parts by weight of the complex was obtained.

Per cent Found, Hg 55.6 C45Hs2O1zS4Hg4 (the neutral salt) requires C69H5sO1oS4Hg8 (the basic salt) requires Hg 55.8

The phenyl mercury complex was a yellowish powder which dissolved in a solution of bis- (naphthalene-2 '7-disulphonic acid) -methane to give a 0.5% solution.

Example I V 1 part by weight of ethyl mercuric acetate was dissolved in 40 parts by weight of hot ethyl alcohol and1.05- parts by weight of anhydrous bis- (naphthalene-Z-sulphonic acid) -methane, dissolved in 10 parts by weight of absolute alcohol added, a creamy gelatinous precipitate separated, which was washed with ether, and dried in vacuo. The ethyl mercury complex analysed as follows:

Per cent Found, Hg 46.5 C25H2406S2Hg2 (the neutral salt) requires C29H3cOaS2I-Ig4 (the basic salt) requires Hg 58.2

This ethyl mercury complex was a brown hygroscopic powder which dissolved ina 10% aqueous solution of bis-(naphthalene-Z-sulphonic acid) -methane to give a 1% solution.

Alternatively a product, doubtless a mixture of the neutral and basic ethyl mercury complexes was obtained by dissolving 4 parts by weight of 6 ethyl mercuric acetate in 8 parts by weight of absolute alcohol and adding 5 parts by weight of a 35% aqueous solution of bis-(naphthalene- 2-sulphonic acid) -methane. A sticky material separated which hardened on standing, this was filtered and dried, yielding 4 parts of the mercury complex. I

Per cent Found, Hg 50.3 C25H24S2O6Hg2 (the neutral salt) requires Hg 45.3 C29H36S2OsHg4 (basic salt) requires Hg 58.2

Example V 28.4 parts by weight of a 16% aqueous solution of the D. S. M. compound prepared by condensing 2-naphthol-6-sulphonic acid with formaldehyde (as disclosed in British Patent No. 547,564) was added to 6.72 parts by weight of phenyl mercury acetate dissolved in parts by weight of hot absolute alcohol, the whole was then heated to boiling and filtered, on concentrating to half bulk 5 parts by weight of the phenyl mercury complex separated on cooling.

Per cent Found, Hg 39.6 CssHziOaszl-lgz (the neutral salt) requires C45H36010S2H8'4 (the basic salt) requires Hg 50.1

The phenyl mercury complex was a reddish brown powder which gave 1.2% solution in a 10% aqueous solution of bis-(Z-naphthol-G-sulphonic acid) -methane and a 0.6% solution in a 10% aqueous solution of bis-(Z-naphthalene-2- sulphonic acid) -methane.

Alternatively 28.4 parts by weight of a 16% aqueous solution of the D. S. M. compound prepared by condensing 2-naphthol-6-sulp-honic acid with formaldehyde was added to parts by weight phenyl mercuric acetatedissolved in 1.40 parts by weight of hot absolute alcohol, the whole was heated to boiling and filtered and then evaporated to approximately half its bulk, on cooling 8 parts by weight of the phenyl mercury complex separated.

Per cent Found, Hg 51.0 C33H2408S2Hg2 (the neutral salt) requires C45HaeO1cS2Hg4 (the basic salt) requires Hg 50.1

The phenyl mercury complex was a reddish powder which gave a 0.5% solution in either a 10% aqueous solution of bis-(2-naphthol-6-sulphonic acid) -methane or a 10% aqueous solution of bis-(naphthalene-Z-sulphonic acid) -methane.

Example VI Per cent Found, As 17.3 C33H32O12N2S2AS2 requires 17.4

This complex dissolved in water to the extent of 1% and gave a clear amber solution. Before use the pH of the solutions was adjusted to 44.5.

Example VII 4.9 parts by weight of a 16% aqueous solution of the D. S. M. compound, prepared by condens- The ethyl mercury complex was a pinkish powder which dissolved to give a 0.6% solution in a aqu o s solution o i either bis-tZ-naphtholfif siilphonic acid) methane or 2 naphthol-(S-sulphonic acid.

Example VIII 2 parts by weight of the pyridine addition compound of pyridyl mercuric acetate, was dissolved in 8 0parts by weight of absolute alcohol, the solution was then treated with a little charcoal and filtered. To the hot alcoholic solution, 3.6 parts by weight of bis-(naphtha1ene-2-sulphonic acid) methane was added with stirring. A precipitate came down, which after standing two hours, was filtered, washed with ether and dried at 110 C.

Per cent E o 7'1 T "I f n C3 1H22S20cN2I-Ig2 The neutral salt required H -T cnHszszoaNiHgi The basic salt requires N The pyridyl mercury complex was a white powder which dissolved to give a 1% solution in a 10% aqueous solution of bis-(napthalene-2-sulphonic acid) -methane or a 0.6% solution in a 10% aqueous solution of naphthalene-2-sulphonic acid.

Examg ile IX Malachite Green zincichloride, bis-(naphthalene2-sulphonic acid) -methane complex:

3.64 parts by weight malachite green zi'n cichloride were dissolved in 120 parts by weight of hot ethyl alcohol and 3.21 parts by weight of the silver salt of bis-(naphthalene-2-sulphonic acid) methane in 32 parts by weight of water added. The solution was left on the steam-bath for several hours to allow the silver chloride formed to coagulate and settle. The solution was then filtered and evaporated down in the presence of a small excess over the equivalent of zinc chloride.

Found: Zinc, 4.1%; nitrogen 3.8%; chlorine 4.4%.

Example X Bis-(sulphosalicylic acid) -methane, phenyl mercury complex:

10.9 parts by weight sulphosalicylic acid was dissolved in 3.6 parts by weight of water by warming gently. 2.1 parts by weight of formaldehyde 40% was then added in three portions while heating on the steam-bath, and the heating continued for a total of 24 hours when the smell of formaldehyde had disappeared. A greyish-green paste was obtained which was taken up in water and filtered from a small quantity of insoluble matter, yielding a15.04% solution of condensation product in the form of a pale straw-coloured liquid.

3.36 parts by weight of phenyl mercury acetate was dissolved in 120 parts by weight o f absolute a cchq n 1. 3 tt b e h qt he a v 15.04% solution added and after warming for 8 some time the greyish powder asfiltered off. This was found to contain 50.1% mercury.

On evaporation of the filtrate a second crop was obtained which contained 50.5% mercury.

Example XI Bis- (1-amino-8-hydroxy-3 6'naphth'alene disulphonic acid) methane phenyl mercury com- 6. parts by weight of pure acid sodium salt of res 1%.: hy r xr a l t a h 3. r t 9 is= nre su nded n 0 Par by WEEPFQ EQ QUWRW f 3 1 Pa t b W 9 centratedhydrochloric acid added. The mixture was filtered and. washed free from chlorides and suspended 25 parts by weight of water, and 3 parts by weight of formaldehyde 40% added. The colour changed slowly from a grey-green sludge to bright yellow and on standing overnight, to a deep orange clear solution. This was heated on the steam bath until the odour of formaldehyde disappeared (several hours) and evaporated to dryness. 5:4 parts glistening deep red scales were obtained. 1.62 parts of this condensation product (by weight) were dissolved in 760 parts by weight 5 0% ethyl alcohol and the mixture with 3.36 parts by weight of phenyl mercury acetate in 60 parts by weight absolute alcohol heated to boiling and filtered from a slight residue. It was then evaporated on the steam-bath and a reddish pb'wde r separated out which was found to contain 42.7% mercury.

I Y I I Per cent C45I I3iO14N'2S4Hg4 requires Hg 45.7 CisI-IasOiaNzSiI-lgl requires Hg 44.7

Example XII Bis-(naphthalene-Z-sulphonic acid) methane, benzyl mercury complex:

2 parts by weight benzyl mercury chloride was dissolved in parts by weight absolute alcohol. To this was added freshly precipitated silver oxide (from 2.8 parts by weight silver nitrate and 48 parts by weight sodium hydroxide).

The suspension was stirred and refluxed for 8 Hours until a few drops on filtering showed no date of chloride, The solution was then filtered hot and 2.63 parts by Weight'of bis- (naphthalene 2-sulphonic acid) methane solution, 49.7% w./w. added to the f ltrate. I After several hours the gelatinous mass was filtered at the pump and dried. V v i We claim: 7

1. As a new compound the bis-phenyl mercury derivative of bis-(nabhthalene-Z-Sulphoni acid) methane. v

2. A method of manufacturing useful products which comprises reacting a compound of the general formula R1QH2R2 with an organometallic compound of the general formula RaMA Where R1 and R2 "each represents a monovalent radical selected from the group consisting of 'COH'3'(.O'H ($0.11. cfln on (scan (alkyl), -.C.,H (0H. sotmooori 12 S sisting of a halogen atom, an amino group and a nitro group, R3 is a radical selected from the group consisting of alkyl, aryl, aralkyl and heterocyclic radicals and alkyl, aryl, aralkyl and heterocyclic radicals having a substituent with a neutral reaction, M is a metal selected from the group consisting of mercury and arsenic and A is a member of the group consisting of acid radicals and groupings forming acid radicals with M.

3. The method defined in claim 2 in which the reaction is carried out with an excess of the compound RICHZRZ.

4. The method defined in claim 2 in which M is mercury.

5. As new compound salts formed by reacting compounds of the general formula R1-CH2--R2 with an organometallic compound of the general formula RaMA where R1 and R2 each represents a monovalent radical selected from the group consisting of:

and said radicals in which a ring hydrogen atom is substituted by a member of the group consisting of a halogen atom, an amino group and a nitro group, R3 is a radical selected from the group consisting of alkyl, aryl, aralkyl and heterocyclic radicals and alkyl, aryl, aralkyl and heterocyclic radicals having a substitutent with a neutral reaction, M is a metal selected from the group consisting of mercury and arsenic and A is a member of the group consisting of acid radicals and groupings forming acid radicals with M.

6. A method as defined in claim 2 in which R3 is an aryl radical.

7. A method as defined in claim 2 in which R3 is an aralkyl radical.

8. A method as defined in claim 2 in which R3 is a heterocyclic radical.

9. A method as defined in claim 2 in which R3 is an aryl radical having a substituent with a neutral reaction.

10. A new compound as defined in claim 5 in which R3 is an aryl radical.

11. A new compound as defined in claim 5 in which R3 is an aralkyl radical.

12. A new compound as defined in claim 5 in which R3 is a heterocyclic radical.

13. A new compound as defined in claim 5 in which R2 is an aryl radical having a substituent with a neutral reaction.

SHEILA EDITH BYWATER. GORDON JAMES PRITCHARD.

REFERENCES CITED The following references are of record in the file of this patent:

UNITED STATES PATENTS Number Name Date 1,986,044 Casaburi Jan. 1, 1935 2,021,137 Stone Nov. 19, 1935 2,215,457 Andersen Sept. 24, 1940 2,326,578 Thuau Aug. 10, 1943 2,344,019 Bostrum Mar. 14, 1944 FOREIGN PATENTS Number Country Date 547,564 Great Britain Sept. 2, 1942 552,751 Great Britain Apr. 22, 1943 

1. AS A NEW COMPOUND THE BIS-PHENYL MERCURY DERIVATIVE OF BIS-(NAPHTHALENE-2-SULPHONIC ACID) METHANE. 